Yeast cells can reproduce via a budding process in which a mother cell buds off a smaller daughter cell. For a time during the process, the mother and daughter look like a three-dimensional figure of eight with a characteristic bottleneck narrowing or “budding neck”. The process forms two genetically identical cells. The astonishing fact is that the daughter cell does not have the same age as the mother cell. The daughter’s internal clock is reset to zero during budding. The research group led by Yves Barral, Professor of Biochemistry, describes how this happens in “Nature”. It means that the biologists have explained a fundamental molecular mechanism that could extend beyond the yeast model.

The researchers observed that pore proteins of the mother cell’s nuclear envelope can move about freely on it until the narrow neck is formed between the mother’s cell nucleus and the newly created daughter nucleus. What is known as a diffusion barrier forms at the constriction point and prevents the proteins from migrating any further. Ageing factors accumulating in the cell nucleus during a mother cell’s life are also unable to pass through the barrier because they are bound to the nuclear pores and are thus anchored in the mother cell. Among other things, these age characteristics include ring-shaped DNA segments. Therefore, molecularly speaking, the new cell is young. In addition, the daughter cell must newly synthesise the proteins to form nuclear pores.

The formation and effectiveness of the diffusion barrier depend in turn on the proteins septin and bud6 respectively. The latter is located at this bottleneck and participates in its formation and maintenance. If bud6 is absent in corresponding yeast mutants, the diffusion barrier does not form and pore proteins including the age factors enter the daughter cell – causing it to have the same age as the mother cell.

However, the purpose of the barrier is not to prolong the life of the cellsD. It ensures that young cells do not start life with an “inherited disadvantage” and can adapt better to possibly changed environmental conditions than their mutant peers of the same species. In a population with mutants, the average life expectancy actually increases because the mother cell gives away part of its age burden to the daughter and rejuvenates itself slightly as a result.

The composition of the barrier remains unclear. Barral suspects that it involves a lipid double layer thicker than a normal one. However, he explains that, “It is very difficult to study lipids in living cells.” There are still no methods, including a staining method, to make them visible.

According to the professor of biochemistry, the results of this study owe a debt of thanks to the “revolution in light microscopy”. This enables specific proteins to be observed in single cells in real time. The studies were carried out in the Light Microscopy Centre of ETH Zurich, a facility established and supported by several professorships.

Barral is in no doubt that their work has tracked down a secret of the ageing not only of cells but of entire organisms. Although they “only” studied yeasts, this living thing is a cell and an organism in one. Asymmetric cell divisions can also be observed in human stem cells. This cell type also resets the age of the “offspring” to zero after cell division. The biochemist stresses that “This is why the results must be interpreted on a much wider scale.” For example one could ask why a baby does not have the same age as its parents. Barral says “It is particularly satisfying when research touches on such central themes and thus embraces philosophical questions.”

Links and references

Shcheprova Z, Baldi S, Buvelot frei S, Gonnet G & Barral Y. A mechanism for asymmetric segregation of age during yeast budding. 2008, Nature, Vol. 454, no. 7205, doi: 10.1038/nature07212.